[Hypertension and endothelin].
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Animals↗
Biomedical subjects
H Kurihara
Publications and source records attributed to H Kurihara.
Expression of the hepatocyte growth factor gene during chick limb development.
It has been shown that mirror-image duplications of the zeugopodia and digits are formed when MRC-5 fibroblasts producing hepatocyte growth factor (HGF) are applied to the anterior region of the chick limb bud (Yonei et al. [1993] Dev. Biol. 160:246-253). To evaluate the role of HGF in limb development, we observed the expression pattern of the HGF gene using in situ hybridization. The HGF gene was expressed in the mesoderm of the limb bud and in the central core region of mandibular arch and maxillary processes at stages 17 to 24. When both wing and leg buds begin to extend distally, the HGF gene is expressed in the mesenchymal cells, but not in the ectodermal cells and somites. Concomitant with establishment of the apical ectodermal ridge, distal mesenchymal cells of the limb bud express the HGF gene intensely with a gradient higher in the distal region. The HGF expression is later confined to the ventral and subapical mesenchyme of the limb bud, although no signal is detectable in the apical and non-ridge ectoderm. However, signal for the c-met proto-oncogene encoding the HGF receptor is not detectable in the limb bud at stages 17 to 24. These results suggest that HGF produced in the limb mesoderm may be involved in initial induction and maintenance of the apical ectoderm during limb development.
Animals↗
Calcified astrocytoma of the amygdalo-hippocampal region in children.
Three pediatric cases of temporal lobe seizure due to calcified glioma of amygdalo-hippocampal region are described. Computed tomography and magnetic resonance imaging showed dense calcification with no postcontrast enhancement in the amygdalo-hippocampal region. Positron emission tomography showed low oxygen metabolism, low glucose metabolism, hypermetabolism of amino acids, and low regional cerebral blood flow in the tumors. Single photon emission computed tomography showed a high accumulation of 201Tl chloride and 123I-isopropyl iodoamphetamine in one tumor, but otherwise low radioisotope uptake. These studies indicated low-grade malignancies. The patients were treated by partial tumor removal and radiotherapy. Histological examination of the tumor specimens showed astrocytoma with interstitial calcification. One patient died due to tumor recurrence, while the others are doing well with minimal seizure. We recommended temporal lobectomy in similar cases to achieve complete remission.
Adolescent↗
Synthesis of 15 alpha-hydroxyestrogen 15-N-acetylglucosaminides.
The synthesis of 15-N-acetylglucosaminides of 15 alpha-hydroxyesterone, 15 alpha-hydroxyestradiol, and 15 alpha-hydroxyestriol (estetrol) is described. The latter two were prepared by condensation of 2-acetamido-1 alpha-chloro-1,2-dideoxy-3,4,6-trio-O-acetyl-D-glucopyranose with appropriately protected 15 alpha-hydroxyestrogens by the Koenigs-Knorr reaction employing cadmium carbonate as a catalyst. Subsequent removal of protecting groups with methanolic potassium hydroxide provided the desired conjugates. 15 alpha-Hydroxyestrone 15-N-acetylglucosaminide was synthesized from the corresponding 15 alpha-hydroxyestradiol derivative by Jones oxidation followed by brief alkaline hydrolysis. These conjugates underwent enzymatic hydrolysis with beta-N-acetylglucosaminidase from Jack beans to produce 15 alpha-hydroxyestrogens.
Acetylglucosaminidase↗
Clinical, microbiological and host defense parameters associated with a case of localized prepubertal periodontitis.
A 4-year-old Japanese boy was referred to Osaka University Dental Hospital because of severe mobility and pain of the right lower primary canine. The canine had severe bone loss and a pocket depth exceeding 5-6 mm. The left lower canine showed slight mobility and moderate alveolar bone loss. The other primary teeth showed no pathogenic findings. The subgingival microflora from the right lower canine was dominated by gram-negative rods, especially capnocytophaga and fusobacterium, while actinomyces sp. were the most common gram-positive bacteria. While neutrophil functions of the patient were within the normal ranges of healthy subjects, some lymphocyte functions such as IL-2 production and IgG and IgM syntheses were lower in the patient. 7 months after the extraction of the right lower primary canine, the patient complained of pain around the right lower primary lateral incisor. In 3-4 weeks, the alveolar bone was lost rapidly and mobility of the lower anterior teeth increased significantly. The primary lateral incisor was extracted and the other primary teeth were treated by sealing and systemic and local administration of antibiotics. After treatment, the lower anterior teeth became less mobile and the gram-positive cocci predominated.
Actinomyces↗
Response of human gingival fibroblasts to prostaglandins.
The effects of various prostaglandins (PGs) on the functions of human gingival fibroblasts (Gin-1 cells; ATCC CRL 1292) were examined by phase-contrast microscopy, cell-counting and radioautographic experiments. Tested PGs were PGA1, PGA2, PGB1, PGB2, PGD2, PGE1, PGE2, PGF1 alpha, PGF2 alpha, PGI2, 6-keto-PGF1 alpha, 9 alpha-11 alpha-methanoepoxy-PGF2 alpha, and thromboxane (TX) B2. PGA1 and PGD2 at 30 microM caused morphological deformation of Gin-1 cells. All the PGs tested at 30 microM suppressed the proliferation of Gin-1 cells in the logarithmic growth phase. Furthermore, all the PGs tested at 10 microM suppressed DNA synthesis, collagen synthesis, and noncollagenous protein synthesis in confluent Gin-1 cells, while exerting no effect on GAG synthesis. The concentrations of PGs used are beyond those found in healthy gingiva. However, in periodontitis the local concentrations of some PGs within the gingiva are expected to be extremely elevated beyond the physiological level. These results suggest that PGs may play an important role as a negative regulator in metabolism and some pathologic gingival conditions by suppressing the functions of gingival fibroblasts.
Cell Division↗
Increased Tyr phosphorylation of ZO-1 during modification of tight junctions between glomerular foot processes.
The slit diaphragms between the glomerular epithelial foot processes represent a variant of the tight junction that are rapidly replaced by typical tight junctions after perfusion with protamine sulfate (PS). To investigate the mechanism of signaling involved, tyrosine phosphorylation of glomerular proteins was analyzed in newborn, PS-treated, and control rats using antiphosphotyrosine immunoglobulin G. In glomeruli of normal adults, phosphotyrosine (Ptyr) staining was confined largely to mesangial cells by immunofluorescence, whereas in newborn and PS-treated rats, the Ptyr signal was dramatically increased in the glomerular epithelium. By immunogold labeling, it was found that newly phosphorylated proteins were concentrated along the newly formed tight junctions (cell-cell junctions) and the basal membrane of the foot processes (cell-matrix junctions). By immunoblotting, several prominent bands were detected with anti-Ptyr in glomerular lysates of controls; in PS-treated rats, additional bands were detected at 225, 180, and 100 kDa. The 225-kDa protein was identified as ZO-1 by immunoprecipitation with anti-ZO-1 followed by immunoblotting with anti-Ptyr. These findings indicate that ZO-1 is one of the targets for tyrosine phosphorylation after PS treatment. They indicate that phosphorylation of tight junction and other proteins occurs during the formation of tight junctions in glomeruli under circumstances where there are rapid changes in epithelial cell shape.
Animals↗
Targeting gene expression to the vascular wall in transgenic mice using the murine preproendothelin-1 promoter.
To develop a system for overexpressing genes in the vascular wall, we created transgenic mice using the reporter gene luciferase and the murine preproendothelin-1 promoter. In vitro analysis suggested that the murine 5'-flanking region contained endothelial-specific elements in a 5.9-kb fragment. Five transgenic mice colonies established from independent founders all exhibited the highest level of luciferase activity in the aorta with up to 8,540 light units per microgram of protein. Immunohistochemistry with anti-luciferase antisera revealed high levels of expression in the endothelial cells of both large and small arteries and lower levels of expression in veins and capillaries. Significant expression was also seen in arterial smooth muscle cells and in select epithelial surfaces which is consistent with the known distribution of endothelin-1 in mammals. The further demonstrate the targeting capability of this system, we overexpressed the lipid-peroxidating enzyme, human 15-lipoxygenase, in the vessel wall of transgenic mice. As with luciferase, expression of active enzyme and immunohistochemical localization in vascular cells were documented in transgenic animals. Hence, this new system can be used to direct expression of molecules to the vascular wall for the purpose of examining the biological significance of either overexpression or inhibition of select proteins.
Animals↗
Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1.
Endothelin-1 (ET-1) is a 21-amino acid peptide with various biological activities including vasoconstriction and cell proliferation. To clarify the physiological and pathophysiological role of ET-1, we disrupted the mouse Edn1 locus encoding ET-1 by gene targeting and demonstrated that ET-1 is essential to the normal development of pharyngeal arch-derived tissues and organs. In this study, we focused on the phenotypic manifestations of Edn1-/- homozygous mice in the cardiovascular system. Edn1-/- homozygotes display cardiovascular malformations including interrupted aortic arch (2.3%), tubular hypoplasia of the aortic arch (4.6%), aberrant right subclavian artery (12.9%), and ventricular septal defect with abnormalities of the outflow tract (48.4%). The frequency and extent of these abnormalities are increased by treatment with neutralizing monoclonal antibodies or a selective ETA receptor antagonist BQ123. At an earlier embryonic stage, formation of pharyngeal arch arteries and endocardial cushion is disturbed in Edn1-/- homozygotes. In situ hybridization confirmed ET-1 expression in the endothelium of the arch arteries and cardiac outflow tract and the endocardial cushion as well as in the epithelium of the pharyngeal arches. Thus, ET-1 is involved in the normal development of the heart and great vessels, and circulating ET-1 and/or other ET isoforms may cause a functional redundancy, at least partly, through the ETA receptor.
Animals↗
Studies on the phenotypic and functional characterization of peripheral blood lymphocytes from patients with early-onset periodontitis.
Juvenile and rapidly progressive periodontitis are grouped under the heading of patients with early-onset periodontitis (EOP). Many studies have investigated host risk factors in the etiology of EOP patients but these remain inconclusive. This study was undertaken to assess the possibility that an abnormality in the systemic lymphocyte subpopulation or function is involved in the etiology of EOP patients. Fourteen (14) patients with juvenile periodontitis (JP), 18 with rapidly progressive periodontitis (RPP), 22 with adult periodontitis (AP), and 33 with a healthy periodontium (HP) participated in this study. Lymphocyte subsets were determined by using panels of monoclonal antibodies (mAbs) and fluorescent flow cytometry. T cell blastogenesis was evaluated by [3H]-thymidine uptake. Pokeweed mitogen induced immunoglobulin G (IgG) and IgM synthesis were detected by sandwich enzyme-linked immunosorbent assay. There were wide distributions of values in all examinations among subjects. No significant difference could be found between the periodontitis patients and HP groups with the exception of a high CD4/CD8 ratio in all patient groups (P < 0.0001) and the depressed percentages of CD3 positive cells noted in the AP patient group (P < 0.0001). These results suggest that the majority of EOP patients do not show significantly different lymphocyte profiles from AP patients and HP subjects, and that lymphocyte cell dysfunctions are not always seen, even in EOP patients.
Adolescent↗
Clinical and laboratory studies on a patient with early onset periodontitis and her family members. A case report.
Extensive clinical, microbiological, hematological, and immunological studies were performed on a patient with early onset periodontitis (EOP) and two other members of the family. The proband, a 27-year-old female, had early onset periodontitis and a high level of serum rheumatoid factors (RF) with no diagnosable medical disease. Her mother had lost all her teeth at the age of 50 because of advanced periodontitis, while her elder sister was unaffected by periodontitis. Neither the proband's periodontally-affected mother nor her unaffected sister exhibited a detectable level of RF. In this study, we examined: 1) serum immunoglobulin G (IgG) antibody titers against putative periodontal pathogenic bacteria; 2) peripheral neutrophil functions; 3) phenotypic analyses of peripheral lymphocyte subpopulations; and 4) peripheral lymphocyte functions (T cell proliferative activity, ability of cytokine [interleukin (IL)-2, tumor necrosis factor-alpha, interferon-gamma, IL-6 and IL-8] and IgG and IgM productivity). High antibody titers to Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Campylobacter rectus were detected in the sera of the proband, as were high serum antibody titers to P. gingivalis in the mother and to C. rectus in the unaffected sister compared to the non-periodontitis affected subjects. The proband also showed enhanced neutrophil chemotaxis; a high percentage of pan-B cells; and high productivity of IL-6, IgG, and IgM compared to individuals who were not periodontally affected. The mother showed slightly low helper/induced T cells (Th/i) suppressor/cytotoxic T cells (Ts/c) ratios due to the elevated count of Ts/c, and high IFN-gamma productivity compared to control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
alpha-Difluoromethylornithine increases the anti-tumor effect of cis-diamminedichloroplatinum in G-XII rat glioma.
The in vivo effects of the single or combined administration of alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, and cis-diamminedichloroplatinum (cisplatin) on the growth of G-XII glioma cells inoculated subcutaneously in rats were tested. Treatment with DFMO or cisplatin significantly decreased the bromodeoxyuridine (BrdU) labeling index of tumor tissues. Combined treatment with DFMO and cisplatin achieved a further significant decrease in the BrdU labeling index. All treatments significantly reduced the tissue levels of N1-acetylspermidine and putrescine, and the ornithine decarboxylase (ODC) activity, but little affected the tissue levels of spermidine and spermine, and the activity of spermidine/spermine N1-acetyltransferase. The reduction of ODC activity by cisplatin treatment may be associated with the anti-tumor effect.
Acetyltransferases↗
Heat shock protein 60 (GroEL) from Porphyromonas gingivalis: molecular cloning and sequence analysis of its gene and purification of the recombinant protein.
Porphyromonas gingivalis is associated with human periodontal disease. We cloned and sequenced the gene for heat shock protein 60 (GroEL, HSP60) from P. gingivalis FDC381. The identified clone carried a 2.6 kb DNA fragment which contained two open reading frames (ORFs) encoding a 9.6- and a 58.4-kDa protein. The translated amino acid sequence of these ORFs showed a high degree of homology with known sequences for GroES and GroEL from several bacterial species and humans. Escherichia coli carrying this clone expressed a 65-kDa protein which was recognized by anti-Mycobacterium leprae HSP60 monoclonal antibody. We purified the 65-kDa protein by DEAE-sepharose chromatography and hydroxyapatite chromatography. This protein was immunogenic and was recognized by sera from a number of patients with periodontal disease. This immunological reactivity and the existence of molecular mimicry between the P. gingivalis GroEL and other HSP homologs may indicate an important role for this molecule in periodontal lesion.
Amino Acid Sequence↗
Massive intestinal bleeding caused by an ileal arteriovenous malformation: report of a case.
We report herein the case of a 43-year-old man in whom gastrointestinal bleeding was found to be caused by a large arteriovenous malformation (AVM) in the ileum. Emergency angiography proved invaluable in disclosing the AVM as the bleeding source, after which the patient was successfully treated by surgery. Although the number of reports of AVM has recently been increasing, ileal AVMs are still relatively rare. Moreover, according to the Japanese literature, no other patient has had such marked and large feeding arteries and draining veins as those in the patient described in this report.
Adult↗
Role of Ca2+ and protein kinase C in shear stress-induced actin depolymerization and endothelin 1 gene expression.
Vascular endothelial cells adapt to changes in blood flow by altering the cell architecture and by producing various substances. We have previously reported that low shear stress induces endothelin 1 (ET-1) expression in endothelial cells and that this induction is mediated by depolymerization of actin fiber. In the present study, we examined the role of Ca2+ and protein kinase C (PKC) in shear stress-induced actin depolymerization and subsequent ET-1 gene expression. Exposure of cultured porcine aortic endothelial cells to low shear stress (5 dyne/cm2) for 3 hours increased the ratio of G-actin to total actin from 54 +/- 0.8% to 80 +/- 1.0%. This shear stress-induced actin depolymerization was completely blocked by chelation of extracellular Ca2+ with EGTA and partially inhibited by intracellular Ca2+ chelation with the tetraacetoxymethyl ester of BAPTA (BAPTA/AM). Pretreatment with staurosporine, a PKC inhibitor, or desensitization of PKC by treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) for 24 hours also resulted in partial inhibition of shear stress-induced actin depolymerization. Although PKC activation by TPA mildly increased G-actin content, the effect of TPA and shear stress on actin depolymerization was not additive. Moreover, shear stress-induced ET-1 gene expression was inhibited by EGTA, BAPTA/AM, and staurosporine to a degree similar to the inhibition of actin depolymerization. In contrast, ET-1 gene expression induced by cytochalasin B, an actin-disrupting agent, was not affected by staurosporine.(ABSTRACT TRUNCATED AT 250 WORDS)
Actins↗
Recurrence of primary intracranial germinomas after complete response with radiotherapy: recurrence patterns and therapy.
Nine germinoma patients are described who developed a recurrence after a complete response to radiation without adjuvant chemotherapy. Extraembryonic tumors producing alpha-fetoprotein and human chorionic gonadotropin were excluded from this study. Four patterns of recurrence are described with respect to mechanism and appropriate treatment. Type I germinoma recurrence, characterized by intracranial recurrence caused by an inadequate initial irradiation field was treated by total craniospinal irradiation. Type II recurrence, characterized by a benign teratoma caused by late growth of the teratoma component was treated by surgery alone. All patients with these patterns of recurrence are still alive. Type III local recurrence is characterized by human chorionic gonadotropin- or alpha-fetoprotein-producing tumors of extraembryonic origin. This pattern of recurrence should be treated by chemotherapy or radiosurgery, because all these patients died. Type IV germinoma recurrence consists of extraneural metastasis without evidence of intracranial recurrence. Two of these patients were treated with chemotherapy. In summary, four patients died after recurrence, whereas the remaining five patients survived. The classification of germinoma recurrence patterns should facilitate the selection of the most appropriate treatment. However, it has been difficult to identify the precise histopathology by biopsy or partial resection alone. Furthermore, chemotherapy is indicated in treating germinomas that have a ventriculoperitoneal shunt because of the risk of extraneural metastases.
Adolescent↗
Molecular basis of leukocyte adhesion molecules in early-onset periodontitis patients with decreased CD11/CD18 expression on leukocytes.
We analyzed the cell-cell adherence related to CD11/CD18 and CD18 mRNA in individuals with decreased CD11/CD18 expression on their neutrophil surface. Epstein Barr virus-transformed B cell lines were developed from one localized juvenile periodontitis (LJP) patient with decreased CD11/CD18 in the peripheral blood neutrophils and without systemic diseases; two siblings with generalized prepubertal periodontitis (GPP) caused by leukocyte adhesion deficiency (LAD); another LJP patient; one localized prepubertal periodontitis (LPP) patient; and two healthy subjects. Adhesion of leukocytes to each other was measured as cluster formation by aggregation assay. The length and the amount of CD18 mRNA expressed in the cell lines were analyzed by Northern blotting using the 32P-labeled CD18 cDNA. The coding region of the mRNA was analyzed by the reverse transcription-polymerase chain reaction method. Base-mismatches between CD18 mRNA and the 32P-labeled RNA probe synthesized from CD18 cDNA were analyzed by RNase protection assay. In the adherence assay, cells from the LJP patients with decreased CD11/CD18 formed more clusters of smaller size and fewer cells than those of the other subjects. The cells from GPP and LAD patients did not aggregate and did not form clusters either in the absence or presence of PMA. There were no differences in the length and the amount of mRNA between the LJP patients and the other subjects, while GPP-LAD patients expressed a small amount of long mRNA. The whole coding region (2,313 base pairs) of all subjects was amplified except for the GPP-LAD patients, and the 5'-region (1,119 base pairs) was amplified from all subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Aggressive Periodontitis↗
Cytokine-dependent synergistic regulation of interleukin-8 production from human gingival fibroblasts.
Human Gingival Fibroblasts (HGF) may have an important role in the orchestration of immuno-participant cells infiltrating the gingiva in response to continuously recurring bacterial infection. To examine the cytokine network regulating HGF-derived interleukin (IL)-8, a potent neutrophil chemotactic cytokine, we analyzed the effects of inflammatory cytokines alone and in combination on IL-8 production by HGF. IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-6, and IL-8 were used as stimulants. HGF secreted IL-8 in a dose-dependent manner after stimulation with either IL-1 beta or TNF-alpha, but not with IFN-gamma or IL-6. Furthermore, IL-8 itself did not affect IL-8 mRNA accumulation in HGF in an autocrine manner. The combination of IL-1 beta and TNF-alpha synergistically enhanced the secretion of IL-8, whereas IFN-gamma suppressed IL-8 secretion by IL-1 beta- or TNF-alpha-stimulated HGF. These effects were also observed at each level of IL-8 mRNA expression in HGF. IL-8 secretion by cytokine-stimulated HGF was not influenced by the inhibition of PGE2 synthesis with indomethacin, indicating that endogenous PGE2 was not involved in IL-8 production by HGF. These results indicate that IL-8 production by HGF is synergistically stimulated by specific cytokines, IL-1 beta and TNF-alpha, and suggest that these stimulatory effects are down-regulated by IFN-gamma at the transcriptional level through PGE2-independent pathways. Thus, neutrophil-mediated processes in periodontal disease may be regulated in part by HGF in the cytokine network of immuno-participant cells.
Chemotaxis, Leukocyte↗